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GYNECOLOGIC CANCER Cervical Cancer from Diagnosis to Survivorship CHAIR Helen Mackay, MD Princess Margaret Cancer Centre, University of Toronto Toronto, ON, Canada SPEAKERS Linda R. Mileshkin, MD Peter MacCallum Cancer Centre Melbourne, Australia Lari B. Wenzel, PhD University of California, Irvine Irvine, CA
NONSURGICAL MANAGEMENT OF CERVICAL CANCER Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond Helen J. Mackay, MD, Lari Wenzel, PhD, and Linda Mileshkin, MD OVERVIEW Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. Cervical cancer remains one of the leading causes of cancerrelated morbidity and mortality worldwide and is the fourth leading cause of cancer death in women. 1 Human papillomavirus (HPV), particularly types 16 and 18, is associated with subsequent development of cervical cancer, with an increased risk also seen among smokers. 2 The incidence and mortality rates of cervical cancer are substantially higher in resource-poor regions of the world; the age standardized incidence of cervical cancer being 1.6 times higher in less developed countries. These regional discrepancies are attributable to reductions made in the incidence of cervical cancer in resource-rich countries with the introduction of widely accessed screening programs. 3 This decline is expected to continue as a result of the implementation and increased availability of vaccination against HPV. 4 These gains,however,remainchallengingtoreplicateinresource-poorregions, which lack the infrastructure and funding to implement screeningandvaccinationprograms,andwhereaccesstotreatment remains an important problem. Within the United States, over 12,000 women will be diagnosed with cervical cancer in 2015 with approximately 4,000 women expected to die from their disease. Cervical cancer is disproportionately more common in women of African American or Hispanic ethnicity and in patients with limited access to health care. 3 Despite the advances in cervical cancer prevention and diagnosis, the outcome for patients diagnosed with later-stage and recurrent disease remains poor. NONSURGICAL MANAGEMENT OF LOCALLY ADVANCED CERVICAL CANCER The use of low-dose chemotherapy concurrent with pelvic radiation has been proven to improve survival, and became the established standard of care for locally advanced cervical cancer after the National Cancer Institute issued a clinical alert in 1999 about the benefıt of chemoradiation compared with radiation alone as observed in fıve randomized clinical trials. 5 The Medical Research Council (MRC) individual patient data meta-analysis found that the addition of concurrent chemotherapy to radiation increased the 5-year overall survival (OS) rate by 6% (hazard ratio [HR], 0.81; 60% vs. 66%). 6 On the basis of the studies in this analysis, weekly cisplatin at a dose of 40 mg/m 2 during pelvic radiation has been adopted as the standard of care for the treatment of locallyadvanced disease. However, the 5-year disease-free survival rate was only 58% in the chemoradiation group, which although superior to 50% with radiation alone, still leaves substantial room for improvement. Identifying Patients Most at Risk of Recurrent Disease The main prognostic factor for outcome in cervical cancer has traditionally been the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination alone. In those with FIGO stage 1B2 or higher, treatment with primary chemoradiation in the recommended approach. 7 In the meta-analysis, the additional benefıt of chemotherapy was seen regardless of age, tumor histology, or grade. However, there appeared to be a lesser degree of benefıt in higher staged tumors, with an absolute 5-year survival benefıt of 10% for women with stages Ib to IIa cervical cancer, 7% for those with stage IIb, and 3% for women with stage III to IVa disease. 6 From the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre/Deptartment of Medicine, University of Toronto, Ontario, Canada; Department of Medicine and Public Health, University of California, Irvine, Irvine, CA; Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: Helen Mackay, MD, Princess Margaret Hospital, 610 University Ave., Toronto, ON M5G 2M9, Canada; email: helen.mackay@uhn.on.ca. © 2015 by American Society of Clinical Oncology. asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK e299
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AMERICAN SOCIETY OF CLINICAL ONCOLO
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American Society of Clinical Oncolo
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Controversies in Neoadjuvant Therap
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Clinical Trials of Precision Medici
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Managing Ovarian Cancer in the Olde
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Updates in the Multimodality Manage
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PEDIATRIC ONCOLOGY Real-Time Molecu
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2015 ASCO Annual Meeting Disclosure
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2015 Educational Book Expert Panel
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James Marshall, PhD Roswell Park Ca
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2015 Annual Meeting Supporters* MIS
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David Yurman Corporate Allies Conqu
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BREAST CANCER Individualizing the A
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MICHAEL A. POSTOW Managing Immune C
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AHN ET AL Making Sense of Current a
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AHN ET AL Pancreatic cancer has bee
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AHN ET AL Disclosures of Potential
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EGIDIO DEL FABBRO tion of precachex
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EGIDIO DEL FABBRO FIGURE 3. Mechani
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STAGE I TESTICULAR GERM CELL CANCER
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SHARON H. GIORDANO These databases
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HEALTH SERVICES RESEARCH AND QUALIT
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INDUSTRY AND ONCOLOGY KEY POINTS F
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INDUSTRY AND ONCOLOGY has been “l
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INDUSTRY AND ONCOLOGY by (covered)
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INDUSTRY AND ONCOLOGY 42. World Hea
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CANCER CARE QUALITY: CURRENT STATE
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MANAGING OLDER PATIENTS WITH ALL Th
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MANAGING OLDER PATIENTS WITH ALL TA
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL ra
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TREATMENT OF PHILADELPHIA CHROMOSOM
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CD19 CAR THERAPY FOR ALL FIGURE 1.
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CD19 CAR THERAPY FOR ALL 5. Zhou G,
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NEW TARGETED THERAPIES FOR iNHL New
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NEW TARGETED THERAPIES FOR iNHL TAB
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HEMATOPOIETIC CELL TRANSPLANTATION
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LEUKEMIA, MYELODYSPLASIA, AND TRANS
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MICHAEL W. DEININGER TABLE 1. Defin
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PEMMARAJU AND MOLITERNO drome (BCS)
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THERAPIES AND INDICATIONS FOR PH-NE
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LUNG CANCER Beyond Second-Line Trea
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BEYOND SECOND-LINE TREATMENT FOR LU
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GERBER, PAIK, AND DOWLATI a tumor t
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GERBER, PAIK, AND DOWLATI squamous
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GERBER, PAIK, AND DOWLATI gression
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LUNG CANCER Updates in the Multimod
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WOODARD AND JABLONS section, becaus
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NASSER HANNA Current Standards and
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NASSER HANNA culty of this task. Va
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LYMPHOMA AND PLASMA CELL DISORDERS
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NOWAKOWSKI AND CZUCZMAN sociated wi
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DAVID W. SCOTT Cell-of-Origin in Di
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CHEAH, OKI, AND FANALE Novel Treatm
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MOREAU AND TOUZEAU Multiple Myeloma
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LYMPHOMA AND PLASMA CELL DISORDERS
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MANAGEMENT OF CLL Up-Front Manageme
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MANAGEMENT OF CLL than 17p-/TP53mut
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MANAGEMENT OF CLL could be associat
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MANAGEMENT OF CLL tion by nonmalign
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MANAGEMENT OF CLL lymphocytic leuke
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PROGNOSTIC FACTORS AND ADJUVANT RAD
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MERKEL CELL CARCINOMA Merkel Cell C
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MERKEL CELL CARCINOMA tions in PIK3
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PERFUSION AND INFUSION IN THE ERA O
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SULLIVAN ET AL FIGURE 1. Relevant S
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SULLIVAN ET AL 17. Halait H, Demart
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SULLIVAN ET AL NRAS-mutant melanoma
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KLEPIN, RODIN, AND HURRIA Treating
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KLEPIN, RODIN, AND HURRIA plication
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KLEPIN, RODIN, AND HURRIA 62. Blanc
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PERIPHERAL NEUROTOXICITY IN CANCER
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PARTRIDGE, JACOBSEN, AND ANDERSEN C
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PARTRIDGE, JACOBSEN, AND ANDERSEN c
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PARTRIDGE, JACOBSEN, AND ANDERSEN w
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PARTRIDGE, JACOBSEN, AND ANDERSEN v
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LESLIE R. SCHOVER Sexual Healing in
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LESLIE R. SCHOVER tinuous ADT in pr
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LESLIE R. SCHOVER 12. Potosky AL, H
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CATHERINE H. VAN POZNAK TABLE 1. Wo
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CATHERINE H. VAN POZNAK (tamoxifen,
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CATHERINE H. VAN POZNAK TABLE 3. FD
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CATHERINE H. VAN POZNAK premenopaus
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SHARI GOLDFARB KEY POINTS Brea
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SHARI GOLDFARB and friction with va
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SHARI GOLDFARB importance both duri
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PATIENT AND SURVIVOR CARE Moving Su
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MAYER ET AL TABLE 1. Quality Metric
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MAYER ET AL to enhance the quality
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MAYER ET AL FIGURE 2. (A) Infertili
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MAYER ET AL efıcial suggests that
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PATIENT AND SURVIVOR CARE The Chall
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BRUERA AND PAICE Choice of Opioid a
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BRUERA AND PAICE toxicity and proce
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BRUERA AND PAICE effective. Basic s
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PEDIATRIC ONCOLOGY Real-Time Molecu
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CARROLL, RAETZ, AND MEYER KEY POINT
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CARROLL, RAETZ, AND MEYER most are
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CARROLL, RAETZ, AND MEYER markers a
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PEDIATRIC ONCOLOGY Translating Surv
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REDUCING THE BURDEN OF LATE EFFECTS
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PROFESSIONAL DEVELOPMENT The Challe
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ADVANCES IN WEBSITE INFORMATION RES
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COMMUNICATION AND TECHNOLOGY: IT’
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PATIENT-REPORTED OUTCOMES IN ONCOLO
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PATIENT-REPORTED OUTCOMES IN ONCOLO
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PROFESSIONAL DEVELOPMENT Trends, An
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CLINICAL ONCOLOGY PRACTICE 2015 FIG
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CLINICAL ONCOLOGY PRACTICE 2015 (6.
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CLINICAL ONCOLOGY PRACTICE 2015 Pro
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ADJUVANT/NEOADJUVANT MEDICAL THERAP
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INDICATIONS FOR ADJUVANT RADIATION
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SARCOMA Latest Advances in Systemic
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SYSTEMIC THERAPY FOR OSTEOSARCOMA A
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SYSTEMIC THERAPY FOR OSTEOSARCOMA A
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RETHINKING TREATMENT FOR CHONDROSAR
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BONE SARCOMAS IN ADULTS local disea
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BONE SARCOMAS IN ADULTS structure a
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SARCOMA Well-Differentiated and Ded
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ABBAS MANJI ET AL ticular region. 7
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ABBAS MANJI ET AL MYXOID (ROUND CEL
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ABBAS MANJI ET AL versus doxorubici
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SHLUSH AND HERSHKOVITZ Clonal Evolu
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SHLUSH AND HERSHKOVITZ FIGURE 1. Ti
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TUMOR BIOLOGY New Strategies to Und
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KNAPP, DHAWAN, AND OSTRANDER in dog
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KNAPP, DHAWAN, AND OSTRANDER TABLE
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KNAPP, DHAWAN, AND OSTRANDER 14. Fe
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SOURBIER, SRINIVASAN, AND LINEHAN M
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SOURBIER, SRINIVASAN, AND LINEHAN F
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SOURBIER, SRINIVASAN, AND LINEHAN T
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Author Index Abbas Manji, Gulam ...
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